Abstract PR014: Evaluating circulating tumor DNA by targeted next generation sequencing as a biomarker in the treatment of localized pancreatic cancer
Authors: Dhavan Shah, Amy Wells, Kevin Dawravoo, John Abad, Arlene D'Souza, Grace Suh, Robert Bayer, Sohail Chaudhry, David Bentrem, Akhil Chawla, Madison Cox
Journal: Cancer Research (2022)

Abstract Introduction: The utility of circulating tumor DNA (ctDNA) as a biomarker in localized pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to characterize the detection of ctDNA by targeted next-generation sequencing (NGS) during treatment for localized PDAC and to evaluate the clinical implication of detection. Methods: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine Cancer Centers between September 2020 and May 2022. During treatment, blood was drawn for targeted NGS ctDNA assessment utilizing the Tempus xF 105 gene panel assay. Three timepoints during the course of treatment were evaluated: at diagnosis prior to treatment, after neoadjuvant chemotherapy (NAC), and after local therapy, which included surgery with or without radiotherapy, or radiotherapy alone. The effect of NAC and local therapy on ctDNA mutational status and its relationship with serum CA19-9 was analyzed. Results: 32 patients who underwent NAC were included in the analysis. 66% of patients received FOLFIRINOX and 34% received Gemcitabine/nab-paclitaxel. The mean length of NAC was 3.1 months. TP53 mutations were the most common mutation detected by targeted NGS (41%), followed by KRAS (G12D/V/R, 13%) and ATM mutations (13%). In 24 patients assessed prior to treatment, 10 (42%) were found to have detectable ctDNA. 11 of 32 (34%) patients had detectable ctDNA following completion of NAC. 22 patients underwent surgery, of which 6 (27%) had detectable ctDNA following NAC and surgery. Of the 10 patients who had detectable ctDNA prior to treatment, 4 (40%) cleared ctDNA after treatment. Patients with detectable ctDNA prior to treatment had higher CA19-9 levels following NAC compared with those with undetectable ctDNA prior to treatment (1244.83 U/ml vs 60.42 U/ml, p = 0.0299). Following NAC, patients with detectable ctDNA had higher CA19-9 levels than those with undetectable ctDNA after NAC (1121.05 U/ml vs 58.89 U/ml, p = 0.0231). 6 of 32 (19%) patients were found to have unresectable disease following NAC and underwent definitive radiotherapy for local control; none of these patients had ctDNA clearance. Conclusion: This is the first reported study demonstrating the value of targeted NGS as a biomarker in the treatment of localized pancreatic cancer. Treatment led to clearance of detectable ctDNA, although the effect was not seen in all patients. Patients with detectable ctDNA prior to treatment had higher levels of CA19-9 following NAC, suggesting that pre-therapy detection may be a predictor of poor serum CA19-9 response after NAC. Given that after NAC, patients with detectable ctDNA had significantly higher serum CA19-9 levels, ctDNA assessment by targeted NGS may be an additional biomarker of treatment response. Taken together, ctDNA detected by targeted NGS is a potential biomarker of treatment response in localized PDAC. Citation Format: Dhavan Shah, Amy Wells, Kevin Dawravoo, John Abad, Arlene D'Souza, Grace Suh, Robert Bayer, Sohail Chaudhry, David Bentrem, Akhil Chawla, Madison Cox. Evaluating circulating tumor DNA by targeted next generation sequencing as a biomarker in the treatment of localized pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR014.